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Acellular ascites fluid (AAF) is rich in signalling molecules and has been proposed to play a role in the induction of chemoresistance. Through\n                    <jats:italic>in vitro<\/jats:italic>\n                    testing of drug sensitivity and by assessing intracellular phosphorylation status in response to mono\u2010 and combination treatment of five EOC cell lines after incubation with AAFs derived from 20 different patients, we investigated the chemoresistance\u2010inducing potential of ascites. We show that the addition of AAFs to the culture media of EOC cell lines has the potential to induce resistance to standard\u2010of\u2010care drugs (SCDs). We also show that AAFs induce time\u2010 and concentration\u2010dependent activation of downstream signalling to signal transducer and activator of transcription 3 (STAT3), and concomitantly altered phosphorylation of mitogen\u2010activated protein kinase kinase (MEK), phosphoinositide 3\u2010kinase (PI3K)\u2013protein kinase B (AKT) and nuclear factor NF\u2010kappa\u2010B (NF\u03baB). Antibodies targeting the interleukin\u20106 receptor (IL6R) effectively blocked phosphorylation of STAT3 and STAT1. Treatments with SCDs were effective in reducing cell viability in only a third of 30 clinically relevant conditions examined, defined as combinations of drugs, different cell lines and AAFs. Combinations of SCDs and novel therapeutics such as trametinib, fludarabine or rapamycin were superior in another third. Notably, we could nominate effective treatment combinations in almost all conditions except in 4 out of 30 conditions, in which trametinib or fludarabine showed higher efficacy alone. Taken together, our study underscores the importance of the molecular characterisation of individual patients' AAFs and the impact on treatment resistance as providing clinically meaningful information for future precision treatment approaches in EOC.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13726","type":"journal-article","created":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T22:59:35Z","timestamp":1725836375000},"page":"81-98","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Patient\u2010derived acellular ascites fluid affects drug responses in ovarian cancer cell lines through the activation of key signalling pathways"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-2118","authenticated-orcid":false,"given":"Katharina","family":"Bischof","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology, Institute for Cancer Research 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